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What we Don’t Know

Some critics claim that all the great questions in science have already been answered or are simply unanswerable. But a leading defender argues that reports of science’s death have been greatly exaggerated.

This fall will mark the thirtieth anniversary of an important milestone in my education. It was then, inspired by a great teacher, David R. Wones, that I declared Course XII, earth science, as my undergraduate major at MIT. To his students, Professor Wones seemed to possess an encyclopedic knowledge of rocks, minerals, geomorphology, and plate tectonics. He demanded much of us, with lengthy lab exercises and exhausting field trips in the New England rain. But his enthusiasm for scientific discovery-his passion to learn the things that we don’t know but might someday find out-was infectious. He rekindled in me the deep curiosity that everyone feels as a child, and he focused that untutored, youthful instinct into an exacting experimental rigor. How shocking and sad, then , to read that I may be one of the last of a breed, for science, we are told, has entered its twilight, the victim of its own success. An eager pack of science watchers, led by science journalist John Horgan, author of The End of Science: Facing the Limits of Knowledge in the Twilight of the Scientific Age (Addison-Wesley, 1996) would have us believe that the end of science is at hand (see “The Twilight of Science” by John Horgan, TR July 1996). We are nearing the time, these observers contend, when we will have deduced all the great laws of nature and learned everything of significance about the natural world that can be learned. There are only so many things to find out, Horgan says, and each discovery brings us closer to closure. J. J. Thompson discovered the electron, so check that off the list. Evolution by natural selection, nuclear reactions, electromagnetic radiation, DNA-soon we’ll know it all.

What rubbish! Such facile claims ignore the nature of the scientific process and the character of the questions it attempts to answer. Horgan is at least honest enough to warn unsuspecting readers that his college studies of literary criticism taught him to write analysis that is not “the final word” but rather “more clever, more interesting than the rest.” Horgan is a clever writer, and he has managed to say something interesting, if exceptionally misleading.

But Horgan’s smoke and mirrors is more than harmless literary legerdemain. By using stylish prose to cast doubt about the future vitality of science, he runs the risk of creating a self-fulfilling prophecy. Why should the public support basic research if nothing of interest is left to discover?

William Harvey, the seventeenth-century English physician who discovered the nature of blood’s circulation, spoke for today’s researchers when he said, “All that we know is still infinitely less than all that remains unknown.” The key to understanding why science is an endless frontier lies not in cataloging what we know but rather in recognizing the vast amount of what remains unknown-the unanswered questions. These questions, which drive basic scientific research, fall logically into three broad categories of inquiry-questions about what exists, how it came to be, and how nature works. As the following summary of today’s leading research demonstrates, those questions are inherently unlimited in scope, and the chain of discovery-and human curiosity that drives the quest for knowledge-shows not the slightest sign of ending.

What’s Out There?

Questions about what exists mark the starting point of science. Scientific explorers of the past reveled in voyaging to exotic lands in pursuit of animal, plant, and mineral specimens. Chemists isolated element after element, physicians dissected diseased corpses, astronomers cataloged countless stars, and physicists scrutinized unusual phenomena associated with electricity and magnetism.

Even after centuries of labors, by most estimates we have identified only one or two percent of all living species on earth, have sampled only the thin outer skin of the planet, and have described only a few of the 80,000 proteins that our bodies produce. We know all 100 or so stable elements of the periodic table, but the number of possible combinations of these elements is for all intents and purposes infinite. Looking outward to space, we observe tens of billions of stars in each of tens of billions of galaxies-perhaps a trillion solar systems exist for every human. There is so much left to discover.

Skeptics would have us believe that the hundreds of thousands of scientists around the world who devote their lives to exploring these domains are like high-tech postage-stamp collectors-filling in a few blanks rather than pursuing interesting research. These skeptics are wrong. The earth, our solar system, and the universe beyond holds wonders to captivate (and profit) the human race for millennia.

Moreover, if the task of describing the tangible universe weren’t enough, it now appears that most of the mass of the universe-as much as 99 percent by some estimates-is missing, evidently consisting of strange matter unlike anything we now comprehend. Within the past two decades astronomers have discovered overwhelming evidence that the universe is littered with dark matter-seemingly invisible stuff that must be out there but can’t be found even with our most powerful telescopes.

Almost all of the universe’s matter that we know about is concentrated in galaxies, which exist on a scale almost beyond comprehension. Each galaxy holds tens to hundreds of billions of stars in a region that may exceed a 100,000 light years in diameter (a light year, the distance light travels in a year, is almost 6 trillion miles). Our own galaxy, the Milky Way, contains all the stars and constellations that are familiar to us in the night sky, but billions of other galaxies are also easily visible with the aid of telescopes.

For astronomers who want to study the nature and distribution of the universe’s mass, galaxies are the logical place to start. These scientists rely on two complementary methods to estimate a galaxy’s mass. The quick and easy way is to count the total number of visible stars (an effort simplified by image-processing computers), and then multiply that number times the average mass per star (a value painstakingly determined from observations and theory). This calculated value is known as the “visible mass” of a galaxy.

Alternatively, astronomers determine the “dynamical mass” of a galaxy by observing how stars move. Specifically, they measure the position and orbital speed of its stars or clouds of gas as they circle about the galactic center, the locus of immense gravitational forces. The more massive the galaxy, the faster its stars must travel in their galactic orbits to keep from falling in, closer to the center. Ultimately, if we have properly accounted for all of a galaxy’s variables, the visible mass should exactly match the dynamical mass.

But in the 1970s astronomers discovered that outer portions of spiral galaxies rotate two to three times faster than they should, based on the gravity produced by stars we can see. The simple equation describing orbits has only three variables: orbital distance, orbital speed, and mass. Two of these variables, orbital distance and speed, can be measured by telescopic observations, so a galaxy’s true mass can be calculated. The conclusion: estimates of mass based on visible stars are wrong; most of a galaxy’s mass is not visible. It follows that most of the matter in the universe is dark and invisible.

Speculation about the nature of dark matter abounds. The first step is to eliminate what dark matter isn’t: It can’t be made of ordinary clumps of matter like snowballs or black holes, because we could detect its effects on light arriving from more distant sources. It can’t be made of electrically charged particles like electrons or protons, because such particles emit telltale electromagnetic radiation. Indeed, the fact that we can’t presently detect dark matter in the laboratory suggests that it must pass right through ordinary collections of atoms.

Faced with these daunting constraints, scientists have postulated a number of weird possibilities for the missing mass-exotic subatomic particles such as massive neutrinos or axions, mini black holes, or clusters of quarks called quark nuggets-but no one knows for sure. Around the world, teams of physicists are struggling to design more sensitive detectors to capture the subtle signals of dark matter. It may take many decades, but researchers are not likely to give up for lack of interest.

If all our present science is based on observations and measurements of a paltry 1 percent of reality’s building blocks-everyday atomic matter-then how can physics be almost over? The search for dark matter, still in its barest infancy, is not a trivial academic pursuit. In fact, the nature and amount of missing mass is closely tied to the ultimate fate of the universe, namely whether the expanding universe’s enormous gravity will eventually cause it to slow and finally collapse back into itself. The missing mass problem thus lies at the heart of our most fundamental attempts to understand the past, present, and future state of the cosmos.

Moreover, how astounding it is to think that the stuff of which we are made and the only matter we know may constitute only a tiny fraction of what exists. We are confronted with so many questions: What is this strange stuff? How can we study it? What laws govern its behavior? And if we can confine and shape this matter to our will, what undreamed of technologies might follow?

How Did All This Come to Be?

Origin questions fascinate today’s scientists, just as they have human thinkers since before recorded history. The origin of the universe remains perhaps the greatest cosmological question, with scientists, philosophers, and theologians all staking a claim to the answer. Locally in the cosmos, the origins of our galaxy and solar system are questions of mythic stature that invite broad speculation and foster intense debate. But of all the origin questions, the origin of life is certainly among the most profound. Fortunately, it is also highly amenable to exploration through experimental science, since it is a chemical process that might be duplicated in the laboratory.

Two complementary research strategies converge on origin of life questions. The quest to create life in the laboratory began in 1952 when University of Chicago professor Harold Urey and graduate student Stanley Miller devised glassware that sent electric sparks though a primordial atmosphere of methane, hydrogen, and ammonia circulating above warm water. Much to their surprise, in a matter of days the simple solution turned from colorless to pink to red to brown as a rich broth of organic molecules formed. These experiments, which in essence work forward in time from the basic carbon compounds that existed 4.5 billion years ago, when the earth first began to form, reveal that the primitive oceans must have become stocked rather quickly with a variety of relatively complex organic molecules. The earliest oceans and sediments may have grown increasingly concentrated in these organic molecules, for there was no life to gobble up the rich mix.

There is still a tremendous gap between Miller and Urey’s sterile soup of organic molecules and a living cell. But that gap may be narrowed by an alternative research strategy that examines the chemical mechanisms of two of the earth’s most primitive single-celled organisms: mycoplasma and cyanobacteria. The smallest of these, mycoplasma cells, are only about one ten-thousandth of an inch in diameter. The least complex life forms known, these cells depend on their environment to supply many kinds of organic nutrients, including amino acids and nucleic acids. Cyanobacteria, in contrast, are larger and more complex single cells, but they have the ability to survive and reproduce entirely from the most basic ingredients-carbon dioxide, nitrogen, and water, plus a few mineral nutrients.

The structural simplicity of mycoplasma and the chemical simplicity of cyanobacteria can illuminate different aspects of early life. For example, the cellular structures and metabolic pathways by which cells extract energy from sugar are common to all life forms, and must have been present in some fashion in the earliest cells. By paring down metabolism to its most basic chemical reactions, scientists hope to glimpse a plausible sequence of events that might have occurred spontaneously, before the first cell began to reproduce.

The origin of life was a historical event, and many details of that history are still preserved in the chemical structures of cells. Through biochemical studies we can deduce and perhaps reproduce some of the chemical steps associated with that event. But even if someday centuries from now we learn every nuance of the origin of life on our planet, who can predict how many alternate chemical pathways to life may have arisen elsewhere in the cosmos? We can imagine no end to the search for the possible myriad origins of life in the universe.

How Does Nature Work?

The third, and arguably most open-ended, type of scientific question seeks to understand the processes by which nature works: how stars evolve, how rocks erode, how cancer develops, how atoms interact, how fungi reproduce-on and on, questions that arise by the millions. Descriptions of the dynamic evolution and interplay of natural systems help us not only understand the past and present but also predict the future of our physical surroundings. Perhaps of more immediate interest, knowledge of how nature works will help us address problems of fundamental importance to our well being. In fact, most of today’s basic scientific research focuses on answering such questions, and the findings are revealing bewildering complexity.

Consider one of the oldest mysteries of science: how a single fertilized egg transforms into a human being. As an embryo develops, cells must adopt exact spatial relations in a precise time-ordered pattern. As the first cell divides again and again, head, gut, legs, and heart assume their unique identities while new generations of cells play the specialized roles of blood, bone, and brain.

How is it possible for the genes in a solitary fertilized egg to contain all the information necessary to produce a complex individual? This question, first explored a century ago by German biologist Wilhelm Roux in microscopic studies of frog embryos, has blossomed into one of the most exciting frontiers of science, engaging thousands of researchers and showing no sign that a complete answer will ever be forthcoming.

Moreover, it’s hard to imagine a scientific question that will have a more complex and lengthy answer. Documenting and describing the countless individual steps that yield a single fly-the rough bristles of its legs, the regimented facets of its eye, the exquisite tracery of its wings-will require thousands of thick volumes, each richly illustrated and dense in the jargon of genetics. For a human being, the volumes might number in the millions, and we are still a long way from knowing what to put in such books.

It may take centuries to learn many crucial details of the developmental processes that sculpt our faces, our bodies, and our minds, but a few underlying principles are beginning to emerge through remarkable laboratory experiments. This science, known as developmental biology, often seems peculiar to casual observers since it focuses largely on what goes wrong rather than what goes right. That’s because it’s almost impossible to track the genetic pathways of development when everything goes according to plan. Even if we could freeze the sequence of events and examine every embryonic cell at every step along the way, too many processes occur simultaneously and too many genes play a role. What’s more, humans develop much too slowly-and the ethics of embryo research are too touchy-to make much progress studying our own species.

Developmental biologists, hoping to learn how humans develop normally, therefore concentrate their efforts on much simpler fast-breeding organisms that develop abnormally. The standard research strategy involves growing countless millions of short-lived animals, most often the fruit fly Drosophila melanogaster, with its convenient 10-to-14-day life cycle. Thousands of scientists spend their entire research lives working on the genetics and development of the fly, the most thoroughly studied of all complex organisms. (A simple species of flat worm, Caenorhabditis elegans, comes in a distant second, followed by small vertebrates such as zebrafish, frogs, and mice.)

Developmental biologists produce a high yield of mutant individuals by exposing breeding flies or their eggs to x-rays or mutagenic chemicals. When a new individual fails to develop, or when it develops with an obvious abnormality, the research team swoops down to identify which gene has gone awry. Step by painstaking step, as critical developmental genes are identified one by one, scientists are beginning to piece together the puzzle of how life develops. But as old mysteries are solved, new ones quickly arise, as demonstrated by the recent progress researchers have made in the following key areas:

Chemical controls in the egg: The development of every complex organism begins long before the sex act, sometimes months or years before egg and sperm unite. For example, each egg must contain a suite of complex chemical messages to guide an embryo’s initial formation. In flatworms, for instance, the egg’s first cell division always results in a larger cell to the front and a smaller cell to the rear. Even if one of those two cells is removed, the next division again yields a larger and a smaller cell in the same orientation. In this way, in fact, the separation of head from tail occurs right from the start by a chemical signal in the egg. But the egg can’t control development forever. After two cell divisions (four cells total) removal of any one cell will result in grievous deformity in the flatworm. Evidently, from that point on, the cells themselves send each other signals that guide development, but exactly how is the subject of further investigation.